My interest in collecting, analyzing and integrating large phenotype datasets began nearly ten years ago with the PhysGen Program for Genomic Applications (http://pga.mcw.edu). This program was focused on understanding the genetic basis of fundamental mechanistic pathways of the heart, lung, kidney, blood and vasculature and achieved this goal by developing two panels of consomic rat strains and ENU-induced mutant strains and physiologically characterizing these unique animal models. Comprehensive characterization of the consomic strains allows for immediate mapping of traits to a particular chromosome without the need for genetic crosses. To test the “functionality” of relevant genes found to be associated with cardiovascular and renal disease in human populations, the PhysGen Knockout program (http://rgd.mcw.edu/wg/physgenknockouts) has been developing 100 knockout strains with phenotypic characterization to test the role of these genes in cardiovascular and renal disease mechanisms.

My current focus is on establishing methods to integrate large phenotypic datasets, such as the PhysGen and PhysGen Knockout phenotyping data, with genomic databases such as the Rat Genome Database. This integration will use standardized nomenclature to link the phenotypic data to the rat genomic sequence, allowing the user to query by gene ontology, phenotype ontology and disease pathway. Developing tools to provide easy access to phenotype data for a variety of strains assists in the identification of appropriate disease models and allows for comparison with human data. Integrated phenotype data sets coupled with genomic resources and emerging SNP based genotypes for hundreds of strains will improve our ability to elucidate the genetic basis of disease.

An additional area of research focus has been on the developing and characterizing rat models for pulmonary diseases, including asthma and pulmonary hypertension. Many of the animal models developed as part of the PhysGen and PhysGen Knockout programs have phenotypes that mimic pulmonary disease traits and are ideal models to further understand the genetic and environmental influence in disease development. Integration of published phenotype data for pulmonary disease traits has allowed us to identify key phenotypes that can be used to characterize strains as disease models and identify missing data sets that would further refine ideal animal models of disease.